RIP1 Regulates Mitochondrial Fission during Skeletal Muscle Ischemia Reperfusion Injury
Background Dynamin related protein-1 (Drp1)-mediated mitochondrial fission relates to ischemia reperfusion (IR) injury, and its association with necroptosis is implied. We hypothesized that receptor-interacting protein 1 (RIP1), a key kinase in necroptosis, acted as an upstream of Drp1-mediated mito...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-06-01
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| Series: | Journal of Investigative Surgery |
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| Online Access: | http://dx.doi.org/10.1080/08941939.2022.2036880 |
| _version_ | 1797684461601554432 |
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| author | Yu Cao Shunli Chen Xiangqing Xiong Lina Lin Wantie Wang Liangrong Wang |
| author_facet | Yu Cao Shunli Chen Xiangqing Xiong Lina Lin Wantie Wang Liangrong Wang |
| author_sort | Yu Cao |
| collection | DOAJ |
| description | Background Dynamin related protein-1 (Drp1)-mediated mitochondrial fission relates to ischemia reperfusion (IR) injury, and its association with necroptosis is implied. We hypothesized that receptor-interacting protein 1 (RIP1), a key kinase in necroptosis, acted as an upstream of Drp1-mediated mitochondrial fission during skeletal muscle IR. Methods Thirty rats were randomized into the SM, IR, NI, MI, and DI group (n = 6). The rats in the SM group were shamly operated, and those in the IR group were subjected to 4-hour ischemia of the right hindlimb that was followed by 4-hour reperfusion. Intraperitoneal administration of Nec-1 1 mg/kg, Mdivi-1 1.2 mg/kg and same volume of DMSO were given before ischemia in the NI, MI and DI groups, respectively. Upon reperfusion, the soleus muscles were harvested to determine morphological changes and the expression of RIP1, total Drp1 and p-Drp1 (Ser616). Moreover, the muscular oxidative stress indicators and plasma muscle damage biomarkers were detected. Results IR led to impaired histopathological structures and mitochondrial fragmentation in the soleus muscle tissue, accompanied with increased muscular oxidative stress and muscle injury biomarkers, which could be similarly alleviated by Mdivi-1 and Nec-1 (p < 0.05). RIP1 and p-Drp1 (Ser616) protein levels were significantly upregulated in the soleus muscle subjected to IR injury, this upregulation was attenuated in the NI group, and Mdivi-1 downregulated the protein expression of p-Drp1 (Ser616) but not of RIP1 (p < 0.05). Conclusion RIP1 functions as an upstream of Drp1-mediated mitochondrial fission in the execution of necroptosis during skeletal muscle IR. |
| first_indexed | 2024-03-12T00:29:59Z |
| format | Article |
| id | doaj.art-463951edeafa4d25b3edaba574dfcc17 |
| institution | Directory Open Access Journal |
| issn | 0894-1939 1521-0553 |
| language | English |
| last_indexed | 2024-03-12T00:29:59Z |
| publishDate | 2022-06-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Investigative Surgery |
| spelling | doaj.art-463951edeafa4d25b3edaba574dfcc172023-09-15T10:21:29ZengTaylor & Francis GroupJournal of Investigative Surgery0894-19391521-05532022-06-013561269127410.1080/08941939.2022.20368802036880RIP1 Regulates Mitochondrial Fission during Skeletal Muscle Ischemia Reperfusion InjuryYu Cao0Shunli Chen1Xiangqing Xiong2Lina Lin3Wantie Wang4Liangrong Wang5Department of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Pathophysiology, Wenzhou Medical UniversityDepartment of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical UniversityBackground Dynamin related protein-1 (Drp1)-mediated mitochondrial fission relates to ischemia reperfusion (IR) injury, and its association with necroptosis is implied. We hypothesized that receptor-interacting protein 1 (RIP1), a key kinase in necroptosis, acted as an upstream of Drp1-mediated mitochondrial fission during skeletal muscle IR. Methods Thirty rats were randomized into the SM, IR, NI, MI, and DI group (n = 6). The rats in the SM group were shamly operated, and those in the IR group were subjected to 4-hour ischemia of the right hindlimb that was followed by 4-hour reperfusion. Intraperitoneal administration of Nec-1 1 mg/kg, Mdivi-1 1.2 mg/kg and same volume of DMSO were given before ischemia in the NI, MI and DI groups, respectively. Upon reperfusion, the soleus muscles were harvested to determine morphological changes and the expression of RIP1, total Drp1 and p-Drp1 (Ser616). Moreover, the muscular oxidative stress indicators and plasma muscle damage biomarkers were detected. Results IR led to impaired histopathological structures and mitochondrial fragmentation in the soleus muscle tissue, accompanied with increased muscular oxidative stress and muscle injury biomarkers, which could be similarly alleviated by Mdivi-1 and Nec-1 (p < 0.05). RIP1 and p-Drp1 (Ser616) protein levels were significantly upregulated in the soleus muscle subjected to IR injury, this upregulation was attenuated in the NI group, and Mdivi-1 downregulated the protein expression of p-Drp1 (Ser616) but not of RIP1 (p < 0.05). Conclusion RIP1 functions as an upstream of Drp1-mediated mitochondrial fission in the execution of necroptosis during skeletal muscle IR.http://dx.doi.org/10.1080/08941939.2022.2036880reperfusion injurydynamin related protein-1mitochondrial fissionreceptor-interacting protein 1necroptosisskeletal muscle |
| spellingShingle | Yu Cao Shunli Chen Xiangqing Xiong Lina Lin Wantie Wang Liangrong Wang RIP1 Regulates Mitochondrial Fission during Skeletal Muscle Ischemia Reperfusion Injury Journal of Investigative Surgery reperfusion injury dynamin related protein-1 mitochondrial fission receptor-interacting protein 1 necroptosis skeletal muscle |
| title | RIP1 Regulates Mitochondrial Fission during Skeletal Muscle Ischemia Reperfusion Injury |
| title_full | RIP1 Regulates Mitochondrial Fission during Skeletal Muscle Ischemia Reperfusion Injury |
| title_fullStr | RIP1 Regulates Mitochondrial Fission during Skeletal Muscle Ischemia Reperfusion Injury |
| title_full_unstemmed | RIP1 Regulates Mitochondrial Fission during Skeletal Muscle Ischemia Reperfusion Injury |
| title_short | RIP1 Regulates Mitochondrial Fission during Skeletal Muscle Ischemia Reperfusion Injury |
| title_sort | rip1 regulates mitochondrial fission during skeletal muscle ischemia reperfusion injury |
| topic | reperfusion injury dynamin related protein-1 mitochondrial fission receptor-interacting protein 1 necroptosis skeletal muscle |
| url | http://dx.doi.org/10.1080/08941939.2022.2036880 |
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